Variant rs76114496 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003922.4(HERC1):c.8088A>G(p.Thr2696Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 1,613,902 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 87 hom. )

Consequence

HERC1
NM_003922.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0260

Variant links:

Genes affected

HERC1 (HGNC:4867): (HECT and RLD domain containing E3 ubiquitin protein ligase family member 1) This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]

HERC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 15-63669656-T-C is Benign according to our data. Variant chr15-63669656-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 435412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.026 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00608 (926/152350) while in subpopulation NFE AF= 0.0105 (711/68036). AF 95% confidence interval is 0.00981. There are 7 homozygotes in gnomad4. There are 440 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC1	NM_003922.4 linkuse as main transcript	c.8088A>G	p.Thr2696Thr	synonymous_variant	40/78	ENST00000443617.7	NP_003913.3	Q15751A0A024R5W0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC1	ENST00000443617.7 linkuse as main transcript	c.8088A>G	p.Thr2696Thr	synonymous_variant	40/78	1	NM_003922.4	ENSP00000390158.2		Q15751

Frequencies

GnomAD3 genomes

AF:

0.00608

AC:

926

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00519

AC:

1293

AN:

249094

Hom.:

AF XY:

0.00499

AC XY:

675

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00959

Gnomad OTH exome

AF:

0.00430

GnomAD4 exome

AF:

0.00899

AC:

13135

AN:

1461552

Hom.:

Cov.:

AF XY:

0.00870

AC XY:

6328

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00176

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00684

GnomAD4 genome

AF:

0.00608

AC:

926

AN:

152350

Hom.:

Cov.:

AF XY:

0.00591

AC XY:

440

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.00597

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	HERC1: BP4, BP7, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.6

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over